Document Detail


A randomized, double-blind, placebo-controlled phase 2 study of α4β2 agonist ABT-894 in adults with ADHD.
MedLine Citation:
PMID:  23032073     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dysregulation of the neuronal nicotinic acetylcholine receptor (NNR) system has been implicated in attention-deficit/hyperactivity disorder (ADHD), and nicotinic agonists improve attention across preclinical species and humans. Hence, a randomized, double-blind, placebo-controlled, crossover study was designed to determine the safety and efficacy of a novel α4β2 NNR agonist (ABT-894 (3-(5,6-dichloro-pyridin-3-yl)-1(S),5 (S)-3,6-diazabicyclo[3.2.0]heptane)) in adults with ADHD. Participants (N=243) were randomized to one of four dose regimens of ABT-894 (1, 2, and 4 mg once daily (QD)) or 4 mg twice daily (BID) or the active comparator atomoxetine (40 mg BID) vs placebo for 28 days. Following a 2-week washout period, participants crossed over to the alternative treatment condition (active or placebo) for an additional 28 days. Primary efficacy was based on an investigator-rated Conners' Adult ADHD Rating Scale (CAARS:Inv) Total score at the end of each 4-week treatment period. Additional secondary outcome measures were assessed. A total of 238 patients were assessed for safety end points, 236 patients were included in the intent-to-treat data set, and 196 were included in the completers data set, which was the prespecified, primary data set for efficacy. Both the 4 mg BID ABT-894 and atomoxetine groups demonstrated significant improvement on the primary outcome compared with placebo. Several secondary outcome measures were also significantly improved with 4 mg BID ABT-894. Overall, ABT-894 was well tolerated at all dose levels. These results provide initial proof of concept for the use of α4β2 agonists in the treatment of adults with ADHD. Further investigation of ABT-894, including higher doses, is therefore warranted.
Authors:
Earle E Bain; Weining Robieson; Yili Pritchett; Tushar Garimella; Walid Abi-Saab; George Apostol; James J McGough; Mario D Saltarelli
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial     Date:  2012-10-03
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  38     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-10-17     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  405-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Attention Deficit Disorder with Hyperactivity / drug therapy*,  epidemiology*
Cross-Over Studies
Double-Blind Method
Female
Humans
Male
Middle Aged
Nicotinic Agonists / therapeutic use*
Receptors, Nicotinic / physiology*
Young Adult
Chemical
Reg. No./Substance:
0/Nicotinic Agonists; 0/Receptors, Nicotinic; 0/nicotinic receptor alpha4beta2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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